1. Field
Aspects of the invention relate to devices and related methods of diagnosing conditions associated with the presence of Helicobacter pylori (H. pylori) in a biological sample, and compositions and related methods for treating Helicobacter pylori caused conditions. α-L-fucosidase 2 may be used as a diagnostic marker and a therapeutic target for H. pylori related diseases.
2. Description of the Related Art
About one-half of the global human population is currently infected with Helicobacter pylori, which mainly colonizes the gastric mucosa. Although this pathogen is a leading cause of gastric malignancies (Peek, et. al., Nat. Rev. Cancer 2002, 2:28-37; Cave, D. R. Gastrointest. Dis. 2001, 12:196-202; Sipponen, et. al., Scand. J. Gastroenterol. Suppl. 1993, 196:3-6), most infected individuals remain asymptomatic or are affected merely by chronic gastritis (Cave, D. R. Gastrointest. Dis. 2001, 12:196-202). About 20% of infected patients develop peptic ulcer, gastric cancer, or malignant lymphoma, revealing potential host defense mechanisms against H. pylori pathogenesis.
As a first step for successful infection, H. pylori adheres to the gastric mucosa of epithelial cells. The microbial and host factors that determine the outcome of colonization have been difficult to define, however, in part because of the genetic diversity among H. pylori strains and among humans. The infection process may rely on the pathogen to establish physical contact with the gastric epithelium through H. pylori adhesins. The H. pylori strains that harbor the gene babA2, which encodes the adhesin BabA, are associated with an increased risk for gastric adenocarcinoma (Gerhard, et al., Proc. Natl. Acad. Sci. USA 1999, 96:12778-12783). In addition, SabA was identified as a sialic acid-binding adhesin that binds several sialylated glycoconjugates, including the tetrasaccharide sialyl Lewis X (sialyl Lex), expressed on gastric mucins during chronic H. pylori-mediated inflammation (Mandavi, et al., Science 2002, 297:573-578). The expression of sialyl Lex in gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori may trigger the host tissue to modify the gastric mucosal glycosylation patterns to express the ligands for bacterial adhesins.
The work done by Gordon and coworkers (Hooper, et al., Proc. Natl. Acad. Sci. USA 1999, 96:9833-9838) demonstrated that Bacteroides thetaiotaomicron, a commensal bacterium of the distal small intestine, can induce host synthesis of a specific glycan structure that the microbe can then utilize as a supply of L-fucose residues. L-Fucose is hydrolytically removed and utilized by the bacteria as a carbon and energy source. Thus, it would be helpful to the art to determine whether L-fucose plays a similar role in the interaction between H. pylori and gastric epithelial cells. A recent study showed that H. pylori induced host cells to overexpress β1,3-N-acetylglucosaminyltransferase (β3GnT5), which indirectly produced more sialyl Lex (Marcos, et al., J. Clin. Invest. 2008, 118:2325-2336), suggesting that the pathogen may induce the host to manufacture specific glycans and to activate transcription of several genes simultaneously.
Although H. pylori is well established as the primary cause of gastritis, duodenal ulcer and gastric cancer, currently there is no clear information regarding if and how host cells interact with H. pylori and if such interactions are dependent on the type of gastric disease.